1. |
- Birgisson, Helgi, et al.
(author)
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Patients with colorectal peritoneal metastases and high peritoneal cancer index may benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
- 2020
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In: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 46:12, s. 2283-2291
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Journal article (peer-reviewed)abstract
- Background: Peritoneal cancer index (PCI) >20 is often seen as a contraindication for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastases (PM) from colorectal cancer. The aim of this study was to compare the overall survival in colorectal PM patients with PCI >20 and PCI <= 20 treated with CRS and HIPEC to those having open-close/debulking procedure only.Methods: All patients with colorectal PM and intention to treat with CRS and HIPEC in Uppsala Sweden 2004-2017 were included. Patients scheduled for CRS and HIPEC were divided into three groups, PCI >20, PCI <= 20, and those not operated with CRS and HIPEC stated as open-close including those treated with palliative debulking.Results: Of 201 operations, 112 (56%) resulted in CRS and HIPEC with PCI <= 20, 45 (22%) in CRS and HIPEC with PCI >20 and 44 (22%) resulted in open-close/debulking. Median survival for CRS and HIPEC and PCI >20 was 20 months (95%CI 14-27 months) with 7% surviving longer than 5 years (n = 3). For CRS and HIPEC and PCI <= 20 the median survival was 33 months (95%CI 30-39 months) with 23% (n = 26) surviving >5years. The median survival for open-close was 9 months (95%CI 4-10 months), no one survived >5years.Conclusion: Patients with PM from colorectal cancer and PCI >20 that were treated with CRS and HIPEC experience a one year longer and doubled overall survival compared with open-close/debulking patients. In addition to PCI, more factors should be taken into account when a decision about proceeding with CRS or not is taken.
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2. |
- Cashin, Peter Harald, 1984-, et al.
(author)
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Secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent colorectal peritoneal metastases
- 2024
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In: Surgery Open Science. - : Elsevier. - 2589-8450. ; 20, s. 45-50
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Journal article (peer-reviewed)abstract
- Background:Secondary treatment of recurrent colorectal peritoneal metastases after previous cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is poorly investigated.Objectives:To evaluate the overall survival outcome of secondary (repeat) CRS + HIPEC compared to palliative treatment in recurrent peritoneal disease.Methods:Patients with colorectal peritoneal metastases treated with an index CRS + HIPEC and subsequently having recurrent peritoneal disease were identified from the prospective Swedish national HIPEC registry. Patients were divided into interventional group (secondary CRS + HIPEC) or palliative group. Multivariable logistic regression, propensity-score matching, and survival outcomes were calculated.Results:Among 575 patients who underwent complete CRS between 2010 and 2021, 208 (36 %) were diagnosed with a subsequent recurrent peritoneal disease. Forty-two patients (20 %) were offered secondary CRS + HIPEC. Propensity-score matching of secondary interventional cases with palliative cases succeeded in 88 % (n = 37) in which female sex, lower peritoneal cancer index at index surgery, longer disease-free interval, and absence of extra-peritoneal metastases were identified as the most relevant matching covariates. Median OS from date of recurrence was 38 months (95%CI 30-58) in the interventional group and 19 months (95%CI: 15-24) in the palliative group (HR 0.35 95%CI: 0.20-0.63, p = 0.0004). Sensitivity analyses confirmed the results. As reference, the median OS from index CRS + HIPEC in the whole colorectal registry (n = 575) was 41 months (95%CI: 38-45).Conclusion:After matching for relevant factors, the hazard ratio for death was significantly reduced in patients who were offered a secondary CRS + HIPEC procedure for recurrent peritoneal disease. Selection bias is inherent, but survival outcomes were comparable to those achieved after the initial procedure.
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3. |
- Cashin, Peter, 1984-, et al.
(author)
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Sequential postoperative intraperitoneal chemotherapy for colorectal cancer with peritoneal metastases : a narrative review
- 2021
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In: Journal of Gastrointestinal Oncology. - : AME Publishing Company. - 2078-6891 .- 2219-679X. ; 12, s. S131-S135
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Research review (peer-reviewed)abstract
- Sequential postoperative intraperitoneal chemotherapy (SPIC) is a chemotherapy abdominal infusion given as a postoperative adjuvant treatment for 6 months after cytoreductive surgery (CRS) for peritoneal surface malignancies. It has most commonly been used in conjunction with ovarian cancer where the SPIC treatment has been integrated with adjuvant systemic chemotherapy. This review investigates the role of SPIC in the setting of colorectal cancer with peritoneal metastases. The focus is on the CRS+SPIC combination treatment with no systemic chemotherapy component. Several cohort studies, several comparative studies, and one randomized trial have been reported with several important endpoints. The following aspects will be covered in this review: overall survival, disease-free survival, morbidity, quality-of-life, and cost-effectiveness. In comparison to systemic chemotherapy alone for isolated resectable colorectal peritoneal metastases, CRS+SPIC is superior concerning overall survival, has no difference in morbidity, is similar in quality-of-life, and SPIC is cast-effective. In comparison to HIPEC, results are conflicting in multivariate analysis; but in a univariate analysis HIPEC (most often combined with systemic adjuvant therapy) appears superior to SPIC alone (no systemic component). The future of SPIC is uncertain. However, a combination of HIPEC and SPIC +/- a systemic chemotherapy component is a possible direction to explore further.
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4. |
- Collin, Åsa
(author)
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Colorectal cancer : Aspects of staging, treatment, recurrence and survival
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Colorectal cancer is the third most common malignancy in the world, and major breakthroughs have been made regarding both surgical and oncological treatment. Still, postoperative complications, such as perineal infections after abdominoperineal resection (APR), are a major cause of morbidity, and distant recurrence rate is nearly 20%. In this thesis, means to improve postoperative infection rates, nodal staging in rectal cancer (and resulting overtreatment through (chemo)radiotherapy), cancer recurrence rates and survival, were investigated. In Paper I, the effects on complication rates, recurrence rates and survival of antibiotics applied locally after an APR, by means of a gentamicin-collagen sponge in the perineal wound, were analysed in a randomized setting. No difference was seen regarding any of the endpoints. The results suggest that local antibiotics can safely be omitted in APRs. Paper II investigated the effects of mechanical bowel preparation (MBP) on cancer recurrence and survival, among colon cancer patients undergoing a colon resection. Data from the Swedish randomized MBP trial were used. After follow-up, no improvement in recurrence rates or overall survival was seen, but cancer-specific survival was improved in the MBP group. In conclusion, MBP might be a prognostic favourable factor for outcome in colon cancer patients. In Paper III, the effect of new national guideline criteria for MRI nodal staging in rectal cancer was assessed, regarding the proportion of clinically positive nodes and staging accuracy, and resulting effects on preoperative (chemo)radiotherapy use. Comparing the two years prior to guideline implementation with the two years after implementation revealed a significant decrease in the proportion clinically positive nodes, but staging accuracy remained low, and (chemo)radiotherapy rates decreased with seemingly no correlation to guidelines. Thus, new guidelines decreased the rate of clinically positive nodes, but nodal accuracy remained poor and nodal staging should perhaps not be a criterion in preoperative treatment decisions. Paper IV investigated the impact of the total mesorectal excision quality, by means of the three Quirke grades, mesorectal (best quality), intramesorectal and muscularis propria (worst quality), on recurrence and survival, and assessed risk factors for intramesorectal or muscularis propria resection. Muscularis propria grade was associated with a higher local recurrence rate, but not with distant recurrence or survival. Several factors were associated with intramesorectal and muscularis propria grade, and more caution is warranted in these patients. In conclusion, this thesis provides insight into treatment choice, and the association of day-to-day treatment details with postoperative complications, recurrence and survival rates, as well as the challenges of nodal staging.
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5. |
- Danielson, Johan, 1975-, et al.
(author)
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Change in Deferring Time Correlate to Improved Female Sexual Function after Anal Sphincter Repair: A Prospective Study
- 2020
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In: Open Journal of Obstetrics and Gynecology. - : Scientific Research Publishing, Inc.. - 2160-8792 .- 2160-8806. ; 10:05, s. 729-737
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Journal article (peer-reviewed)abstract
- Background: Many women suffer from sexual problems after anal sphincter tears due to obstetric trauma. Aim: The study aimed to assess changes in sexual function after anal sphincter repair. Methods: The study was a non-randomized prospective observational cohort study. Inclusion of the study was done at the University Hospital, Uppsala, Sweden, between 2002 and 2007. Thirty-nine consecutive female patients admitted for anal sphincter repair were invited to the study. Twenty patients accepted and were included, four were lost to follow up and one was unevaluable (due to the formation of a stoma) leaving a study group of 15 patients. The patients were assessed with questionnaires before surgery and at three and 12 months after surgery. Outcomes: Change in reported sexual activity and dyspareunia. Results: Before surgery, 12/15 patients reported that their sexual life was impaired due to anal incontinence. The corresponding figure at 12 months was 9/15 (p = 0.43). Three patients remained sexually inactive throughout the study, five patients increased their sexual activity and one had decreased activity. Out of the 12 who were active, four stated dyspareunia at baseline, and only one reported dyspareunia at 12 months. The mean Miller incontinence scores at baseline and 12 months were 10.1 and 8.7, respectively. The change in incontinence score did not differ between those with decreased, stable or increased sexual activity. However, there was a definite correlation (r = 0.54 - 0.60, p < 0.05) between change in sexual function and deferring time for stool. Clinical Implications: Operative management of anal sphincter tears alone is not curative for sexual problems due to anal incontinence but can be a part of the treatment. Strengths and Limitations: The study is a prospective study of sexual function. The limitations are that the questionnaires were not validated due to lack of such questionnaires at the time of the study and that the study population is quite small. Conclusion: Patients with a sphincter injury and fecal incontinence often have an impaired sexual function. Increased deferring time for stools after surgery increases the likelihood of improved sexual function.
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6. |
- Danielson, Johan, 1975-, et al.
(author)
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Injectable bulking treatment of persistent fecal incontinence in adult patients after anorectal malformations
- 2020
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In: Journal of Pediatric Surgery. - : W B SAUNDERS CO-ELSEVIER INC. - 0022-3468 .- 1531-5037. ; 55:3, s. 397-402
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Journal article (peer-reviewed)abstract
- Background/Purpose: Injectable bulking therapy has emerged as a treatment for fecal incontinence (IT, however there are no studies including adult patients with anorectal malformations (ARM). This study aimed to evaluate non-animal stabilized hyaluronic add with dextranomer (NASHA/Dx) for the treatment of adult ARM patients with persistent FI.Methods: Seven adults with ARM and incontinence to loose stool at least once weekly and without rectal or mucosal prolapse were treated with anal NASHA/Dx injection. They were evaluated preoperatively, at 6 and 18 months with a bowel function questionnaire and a 2-week bowel diary as well as FTQL and SF-36 quality of life questionnaires.Results: Before treatment, the mean number of incontinence episodes over 2 weeks was 20.7 (median 16, range 8-52). At 6 months, the corresponding figures were 53 (median 4, range 0-19, p = 0.018), and at 18 months the figures were 4.3 (median 2, range 1-20,p = 0.018). An improved physical function in SF-36 from 74.3 at baseline to 86.4 at 6 months was noted (p = 0.04). No serious adverse events occurred.Conclusions: NASHA/Dx is a promising treatment option for selected adult patients with persistent Ft after ARM. Longer follow up of larger patient series and studies on patients in adolescence is needed.
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7. |
- Dranichnikov, Paul, MD, PhD Candidate, 1980-, et al.
(author)
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Coagulopathy and Venous Thromboembolic Events Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy
- 2021
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In: Annals of Surgical Oncology. - : Springer Nature. - 1068-9265 .- 1534-4681. ; 28:12, s. 7772-7782
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Journal article (peer-reviewed)abstract
- Background Coagulopathy after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is recognized but few details have been studied.Objectives The aim of this study was to investigate changes in coagulation biomarkers and their predictive ability for venous thromboembolism (VTE).Methods Patients undergoing CRS and HIPEC at Uppsala University Hospital, Sweden, from 2004 to 2014 were included in a prospective study of coagulation biomarkers. Prothrombin time international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), fibrinogen, antithrombin, D-dimer, and platelets were sampled on postoperative days 1, 2, 5, and 10. Logistic regression analysis was used to evaluate predictive capacity for coagulation-related complications.Results Overall, 380 patients were included (214 females, mean age 56 years); 38 patients had a history of thromboembolism and 57 were active smokers. Mean perioperative blood loss was 1228 mL and 231 (61%) received perioperative blood transfusions. PT-INR and APTT were elevated directly after surgery but returned to normal levels on postoperative day 5. Conversely, fibrinogen, platelet count, D-dimer, and antithrombin increased by postoperative day 5 and continued to increase up to day 10. There were 23 radiologically verified cases of VTE within 6 months. The multivariate analysis identified a completeness of cytoreduction score of 2-3 (p = 0.047) and day 2 D-dimer (p = 0.0082) as independent risk factors for postoperative VTE.Conclusion Significant postoperative changes in coagulation biomarkers occur with dynamic changes over 10 days postoperatively. The incidence of symptomatic VTE was low. Residual tumor at completion of surgery and elevated D-dimer on day 2 were independent risk factors for postoperative VTE.
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9. |
- Dranichnikov, Paul, MD, PhD Candidate, 1980-
(author)
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HIPECology : Aspects of Postoperative Morbidity Following the HIPEC Procedure
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Peritoneal surface malignancy (PM), regardless of the dissemination site, was once considered a terminal condition. However, the introduction of a surgical approach with cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) with or without early intraperitoneal chemotherapy (EPIC) shifted the attitude from managing the symptoms of PM to disease treatment with curative intent. The magnitude of this combined therapy leaves the patients at risk for a diverse range of postoperative morbidities. Moreover, some small cohort studies argued that combining HIPEC with EPIC is associated with a higher risk of postoperative complications compared to HIPEC alone. The overall aim of the thesis was to investigate postoperative morbidity following the management of PM with CRS and HIPEC ± EPIC.We investigated readmission morbidity within 6 months after CRS and HIPEC, using a national population-based register. The results of this study showed that morbidity causing HIPEC-related readmission was higher than expected, with almost half of the interventions occurring outside the HIPEC centre. Gastric resection and advanced age are independent predictors of morbidity and readmission. We analyzed postoperative coagulopathy and the risk for venous thromboembolic events (VTE) in a prospective study. Results revealed that significant postoperative changes in coagulation biomarkers occur with dynamic changes over 10 days postoperatively. The incidence of symptomatic VTE was low. Residual tumor at completion of surgery, and elevated D-dimer on day 2, were independent risk factors for postoperative VTE. Postoperative morbidity following HIPEC + EPIC was compared to morbidity following HIPEC alone in our propensity score matched study. Results showed that HIPEC + EPIC is associated with a prolonged hospital stay (LOS), but there was no statistically significant relevant increase in postoperative morbidity, reoperation rate or incidence of readmission. Finally, we also analyzed the impact of different strategies of intraoperative fluid management during CRS and HIPEC on postoperative outcomes. Goal-directed therapy (GDT) is associated with significantly improved LOS despite an increase in morbidity in some patients. GDT management does not affect the postoperative risk for hemorrhage, although the choice of an oxaliplatin-based HIPEC does. Personalized GDT based on patients’ characteristics and surgery should be utilized during the management of CRS and HIPEC patients.
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10. |
- Dranichnikov, Paul, MD, PhD Candidate, 1980-, et al.
(author)
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Morbidity following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastases with or without early postoperative intraperitoneal chemotherapy : A propensity score matched study
- 2022
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In: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 48:7, s. 1598-1605
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Journal article (peer-reviewed)abstract
- Background: Combining hyperthermic intraperitoneal chemotherapy (HIPEC) treatment with early postoperative intraperitoneal chemotherapy (EPIC) may increase postoperative morbidity. This study aims to investigate postoperative morbidity after HIPEC+EPIC compared with HIPEC alone in patients with peritoneal metastases (PM).Materials and methods: This is a retrospective propensity score matched cohort study. All patients undergoing PM treatment at Uppsala University Hospital between February 2004 and December 2014 were included. Propensity score matching with a 1:1 ratio was performed using sex, primary tumor site, preoperative chemotherapy, peritoneal cancer index, completeness of cytoreduction score, and HIPEC regimen. Length of hospital stay, morbidity, reoperation rate, and readmission rate within 6 months were selected as endpoints.Results: A total of 390 consecutive patients were divided in two arms: HIPEC+EPIC (n = 115) and HIPEC alone (n = 275). The propensity score matching (n = 190) was successful with balanced covariates: 95 patients/arm. The length of stay (LOS) was longer in the HIPEC + EPIC group in the total cohort (30 vs 24 days, p < 0.001), with a trend towards significance in the propensity matched group (29 vs 25 days, p = 0.062). No other differences in endpoints were found.Conclusion: HIPEC+EPIC is associated with a prolonged hospital stay, but with no statistically significant relevant increase in postoperative morbidity, reoperation rate or incidence of readmission.
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